Abstract
Problem
KAI1 is a metastatic suppressor gene. The expression of KAI1 in cancer cells results in reduced cell motility and invasiveness. A cDNA clone of VANGL1, a member of the tetraspanin protein family that specifically interacts with the COOH-terminal cytoplasm domain of KAI1, was isolated and renamed KITENIN (KAI1 COOH-terminal interacting tetraspanin). KITENIN is reported to promote metastasis in a mouse colon cancer model. The purpose of this study was to investigate tumor invasiveness and early lung metastasis by KITENIN in murine floor of mouth cancer model.
Methods
The cDNA of KITENIN and the vector only were transfected into the SCC VII (mouse squamous cell carcinoma cell line) cells. The transfections were performed using the FuGENE 6 transfection reagent. The suspension of 5 × 105/? viable KITENIN- or vector-transfected SCC VII cells were injected into the floor of mouth of C3H/HeJ syngeneic mice deep to the mylohyoid muscle via an intra-oral approach. From the 1st week to 6th week after injection, tumor, lung, liver, and brain tissues were obtained from six mice each group every week and were evaluated under the light microscope.
Results
On each group, the tumor invaded to superficial musculature of floor of mouth, deep musculature of floor of mouth, salivary gland, perineural tissue, bone, and skin sequentially. Lung metastases started from peripheral and localized region and moved to central and diffuse lung tissues. Earlier and more aggressive tumor invasion to deep floor of mouth musculature, salivary gland, perineural tissue, bone, and skin was observed in KITENIN-transfected group than in vector group. Earlier and more diffuse lung metastasis was observed in KITENIN group.
Conclusion
KITENIN enhanced tumor invasion and lung metastasis in murine floor of mouth squamous carcinoma model.
Significance
An antisense KITENIN strategy could be used to inhibit distant metastasis and progression in head and neck squamous cell carcinoma.
Support
This study was supported by a grant CUHRICM-CRI07038-1.
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